Solubility and Mixing Thermodynamic Properties of Capecitabine in Five Acetic Acid Esters at Various Temperatures

Abstract

In pharmaceutical industry, capecitabine is often purified by crystallization from acetic esters. In this work, by using laser dynamic isothermal method, the solubility of capecitabine in methyl acetate from 278.15 to 313.15 K and ethyl acetate, n-propyl acetate, butyl acetate, n-amyl acetate from 278.15 to 323.15 K were measured under atmospheric pressure. The measured solubility data were all correlated by the modified Apelblat equation, λh equation, non-random two liquid (NRTL) and Wilson models. The solubility data can be well correlated with the four thermodynamic models. Based on the solubility data and Wilson model, the mixing entropy, mixing enthalpy and mixing Gibbs energy were evaluated. Besides, the logarithm of activity coefficient lnγ1 of capecitabine in the studied saturated solutions were also calculated with the NRTL and Wilson models. The positive values of lnγ1 mean that the repulsive interactions exist between capecitabine and the corresponding solvents, and the solutions system positively deviate from Raoult’s law. This work can give fundamental data for the crystallization and purification of capecitabine from acetic esters.